In silico and functional analysis identifies key gene networks and novel gene candidates in obesity-linked human visceral fat.

Objective: Visceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk, and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene regulatory networks in human visceral obesity have been lacking.

Methods: We analyzed gene regulatory networks in human visceral adipose tissue (VAT) from 48 and 11 Chinese patients with and without obesity, respectively, using gene coexpression and gene regulatory network construction from RNA-sequencing data.

Shortened sleep duration impairs adipose tissue adrenergic stimulation of lipolysis in postmenopausal women.

Objective: The objective of this study was to examine the changes in adipose tissue lipolytic capacity and insulin signaling in response to shortened sleep duration (SSD) in postmenopausal women.

Methods: Adipose tissue from a randomized crossover study of nine healthy postmenopausal women (mean [SD], age: 59 [4] years; BMI: 28.0 [2.

GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists.

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level.

Thyroid Function Test in Preterm Neonates: Normative Data.

Introduction: Initial surge of thyroid-stimulating hormone (TSH) in neonates increases free and total triiodothyronine (T3) and tetraiodothyronine (T4) in 24-36 hours following birth, and the effect then gradually wanes off. As somatic and intellectual development is dependent on normal thyroid function especially in infancy, normative data in these children may be of immense value to diagnose hypothyroidism in this subset of infants. Comprehensive normative values of thyroid function parameters in preterm neonates are scarcely available.

Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH).

Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo.

Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH.

GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene.

GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers.

Review of the Different Outcomes Produced by Genetic Knock Out of the Long Non-coding microRNA-host-gene MIR22HG versus Pharmacologic Antagonism of its Intragenic microRNA product miR-22-3p.

Background: Publications reveal different outcomes achieved by genetically knocking out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharma-cologic antagomirs specifically targeting the guide strand of such intragenic microRNA. This suggests that lncMIRHGs may perform diverse functions unrelated to their role as intragenic miRNA precursors.

Objective: This review synthesizes in silico, in vitro, and in vivo findings from our lab and others to compare the effects of knocking out the long non-coding RNA MIR22HG, which hosts miR-22, versus administering pharmacological antagomirs targeting miR-22-3p.

Dichotomous transactivation domains contribute to growth inhibitory and promotion functions of TAp73.

The transcription factor p73, a member of the p53 tumor-suppressor family, regulates cell death and also supports tumorigenesis, although the mechanistic basis for the dichotomous functions is poorly understood. We report here the identification of an alternate transactivation domain (TAD) located at the extreme carboxyl (C) terminus of TAp73β, a commonly expressed p73 isoform. Mutational disruption of this TAD significantly reduced TAp73β's transactivation activity, to a level observed when the amino (N)-TAD that is similar to p53's TAD, is mutated.

Functional and Multi-Omics Effects of an Optimized CRISPR-Mediated FURIN Depletion in U937 Monocytes.

The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal and pathological biological processes such as infectious diseases, cancer and cardiovascular diseases. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant plaque reduction and alterations in macrophage function. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) knockout clones in U937 monocytic cells using lipotransfection-based procedures and a dual guide RNA delivery strategy.

Accelerated onset of diabetes in non-obese diabetic mice fed a refined high-fat diet.

Aim: Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non-obese diabetic (NOD) mice.

Methods: Female NOD mice were fed either unrefined diets or matched refined low- and high-fat diets.

Pregnane X receptor knockout mitigates weight gain and hepatic metabolic dysregulation in female C57BL/6 J mice on a long-term high-fat diet.

Obesity is a significant risk factor for several chronic diseases. However, pre-menopausal females are protected against high-fat diet (HFD)-induced obesity and its adverse effects. The pregnane X receptor (PXR, NR1I2), a xenobiotic-sensing nuclear receptor, promotes short-term obesity-associated liver disease only in male mice but not in females.

Covalently-Bonded Laminar Assembly of Van der Waals Semiconductors with Polymers: Toward High-Performance Flexible Devices.

Van der Waals semiconductors (vdWS) offer superior mechanical and electrical properties and are promising for flexible microelectronics when combined with polymer substrates. However, the self-passivated vdWS surfaces and their weak adhesion to polymers tend to cause interfacial sliding and wrinkling, and thus, are still challenging the reliability of vdWS-based flexible devices. Here, an effective covalent vdWS-polymer lamination method with high stretch tolerance and excellent electronic performance is reported.

Selected Area Manipulation of MoS via Focused Electron Beam-Induced Etching for Nanoscale Device Editing.

We demonstrate direct-write patterning of single and multilayer MoS via a focused electron beam-induced etching (FEBIE) process mediated with the XeF precursor. MoS etching is performed at various currents, areal doses, on different substrates, and characterized using scanning electron and atomic force microscopies as well as Raman and photoluminescence spectroscopies. Scanning transmission electron microscopy reveals a sub-40 nm etching resolution and the progression of point defects and lateral etching of the consequent unsaturated bonds.

Estrogen receptor-related receptor (Esrra) induces ribosomal protein Rplp1-mediated adaptive hepatic translation during prolonged starvation.

Protein translation is an energy-intensive ribosome-driven process that is reduced during nutrient scarcity to conserve cellular resources. During prolonged starvation, cells selectively translate specific proteins to enhance their survival (adaptive translation); however, this process is poorly understood. Accordingly, we analyzed protein translation and mRNA transcription by multiple methods and to investigate adaptive hepatic translation during starvation.

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity.

Objective: Visceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene-regulatory networks in human visceral obesity are lacking.

Methods: We analyzed gene-regulatory networks in human visceral adipose tissue (VAT) from 48 obese and 11 non-obese Chinese subjects using gene co-expression and network construction with RNA-sequencing data.

An optimized method for gene knockdown in differentiating human and mouse adipocyte cultures.

Adipocyte cultures are a mainstay of metabolic disease research, yet loss-of-function studies in differentiating adipocytes is complicated by the refractoriness of lipid-containing adipocytes to standard siRNA transfections. Alternative methods, such as electroporation or adenovirus/lentivirus-based delivery systems are complex, expensive and often accompanied with unacceptable levels of cell death. To address this problem, we have tested two commercially available siRNA delivery systems in this study using a multi-parameter optimization approach.

Integrated Care for Type 1 Diabetes: The West Bengal Model.

Introduction: A structured dedicated health programme for Type 1 diabetes mellitus (T1DM) has been initiated in the state of West Bengal, India.

Aim: The aim is to provide comprehensive healthcare to all children, adolescents and young adults living with T1DM, along with the provision of free supply of insulin, glucose measuring devices, blood glucose test strips, and other logistics. The strategic framework for programme implementation is to utilise the infrastructure and manpower of the already existing non-communicable disease (NCD) clinic under National Health Mission.

Corneal Confocal Microscopy Identifies Structural Small Fibre Abnormalities in an Adolescent with Type 1 Diabetes and Impaired Awareness of Hypoglycaemia.

Impaired awareness of hypoglycaemia (IAH) is present in around 25-40% of individuals with type 1 diabetes mellitus (T1DM). Herein, we present a case of an adolescent with T1DM and IAH who had worse corneal nerve parameters compared to a T1DM adolescent without IAH. Small fibre abnormalities detected by corneal confocal microscopy in an objective easy-to-perform non-invasive test might be a surrogate indicator of underlying autonomic dysfunction in T1DM and IAH.

Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis.

Background: Once-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials.

Methods: Seven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included.

Thalidomide-Induced Primary Amenorrhea in a Patient With HbE/Beta-Thalassemia.

An 18-year-old girl was evaluated for primary amenorrhea. She was diagnosed with hemoglobin E (HbE)/beta-thalassemia during childhood and needed blood transfusions every month to maintain adequate hemoglobin levels. She was started on thalidomide to reduce her transfusion requirements at 12 years of age and became transfusion independent after 6 months.

Spectrum of Adrenal Dysfunction in Hemoglobin E/Beta Thalassemia.

Background: Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied.

Aims And Objectives: In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements.

Methods: In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated.